Cytokines impart signals to cells to regulate the immune response, control cell proliferation and differentiation and to regulate the operation of the cytokine network. However, the pleiotropic nature of cytokines is such that in addition to their beneficial effects, cytokines can also induce adverse side effects such as alteration of normal cell growth, undesirable modulation of the functional activity of other cytokines or other unwanted immune effects such as severe inflammation, fever, malaise, nausea or modulation of haemopoiesis.
Inflammation is a particularly important physiological process with effects ranging from minor discomfort to life threatening situations. Macrophages are the key cells in chronic inflammatory lesions which produce a range of inflammatory and pro-inflammatory mediators such as Tumour Necrosis Factor .alpha. (TNF-.alpha.) and Interleukin-1 (IL-1). TNF-.alpha. and IL-1 are proposed to be associated with rheumatoid arthritis, inflammatory bowel disease, Crohns disease, type I diabetes, multiple sclerosis, psoriasis and chronic obstructive lung disease, such as asthma, chronic bronchitis, emphysema and chronic obstructive airway disease. It has been previously proposed to use anti-inflammatory glucocorticoids, which act, at least in part, to suppress macrophage production of TNF-.alpha., IL-1 and other pro-inflammatory mediators. However, although effective, the use of anti-inflammatory glucocorticoids poses therapeutic difficulties given that their receptors are widespread in the body.
In work leading up to the present invention, the inventors proposed to adopt a strategy of lowering monocyte/macrophage levels and/or reducing their level of activation, especially at a site of inflammation in the treatment of inflammatory conditions. The method developed by the instant inventors does not require knowledge of which pro-inflammatory mediator(s) is (are) more relevant to a particular inflammatory condition than another pro-inflammatory mediator.